Ketogenic diets consumed during radio-chemotherapy have beneficial effects on quality of life and metabolic health in patients with rectal cancer.

PURPOSE: Interest in ketogenic diets (KDs) as complementary nutritional treatments for cancer patients is rising, although some skepticism about their safety exists. We, therefore, studied the effects of KDs on quality of life and blood parameters in rectal cancer patients undergoing radio-chemotherapy. METHODS: EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters were obtained prior to, in the middle of and at the end of radiotherapy within the KETOCOMP study (ClinicalTrials.gov Identifier: NCT02516501). A total of 18 patients consuming a KD were compared to 23 patients consuming their standard diet (SD). Baseline-end differences were measured using Wilcoxon tests, and repeated measures analysis was performed using linear mixed effects models. RESULTS: Eighty-nine percent of patients on the KD reported subjectively feeling good or very good, but roughly half of them rated the daily routine implementation as difficult. Only the SD group experienced significant declines in physical and role functioning, while the KD group improved in role (p = 0.045), emotional (p = 0.018) and social functioning (p = 0.009).Urinary frequency, buttock pain and fatigue significantly increased in the SD group, but to a much lesser extent in the KD group. Several biomarkers of metabolic health (gamma-glutamyl-transpeptidase, triglyceride-glucose index, HDL cholesterol/triglyceride ratio, and free T3) improved in the KD, but not the SD group. CONCLUSIONS: Despite being perceived as difficult to implement by ≈50% of patients, KDs are feasible as complementary therapies alongside radio-chemotherapy and associated with subjective well-being. The hypothesis that they exert beneficial effects on quality of life and metabolic health in rectal cancer patients is supported by our data. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02516501, registered Aug 6th 2015.

Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients.

BACKGROUND & AIMS: Obesity and low muscle mass are associated with worse outcomes of colorectal cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in rectal cancer patients undergoing radiotherapy. METHODS: Patients with non-metastasized rectal cancer were allocated to either the KD (N = 24) or the SD (N = 25) group during radiotherapy. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Pathologic response in patients undergoing neoadjuvant treatment was evaluated at the time of surgery. RESULTS: A total of 18 KD and 23 SD patients completed the study and were eligible for analysis. The SD group experienced no noteworthy changes in any body composition parameter. In contrast, patients in the KD group lost significant amounts of body weight and fat mass, averaging 0.5 and 0.65 kg/week (p < 0.0001). There was a rapid loss of intracellular water consistent with initial intramuscular glycogen and water depletion, but skeletal muscle tissue was conserved. Pathological tumor responses were somewhat greater in the KD group, with a larger mean Dworak regression grade (p = 0.072) and larger percentage of near-complete (yT0N0 or yT1N1) responses (43 versus 15%, p = 0.116) that almost reached statistical significance in intention-to-treat analysis (50% versus 14%, p = 0.018). CONCLUSIONS: In rectal cancer patients undergoing curative radiotherapy, a KD significantly reduced body weight and fat mass while preserving skeletal muscle mass. We could demonstrate a trend for KDs contributing synergistically to pathological tumor response, a finding in line with preclinical data that warrants future confirmation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.

Perioperative chemotherapy with or without epidermal growth factor receptor blockade in unselected patients with locally advanced oesophagogastric adenocarcinoma: Randomized phase II study with advanced biomarker program of the German Cancer Society (AIO/CAO STO-0801).

BACKGROUND: Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab. The primary end-point was the histological response rate after neoadjuvant therapy. The expression status and gene copy number of EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Plasma samples were collected before the first cycle of neoadjuvant chemotherapy. RESULTS: Overall, 160 patients (80 versus 80) were eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of R0-resection, percentage of patients with downstaging to ypT0-2 at pathohistological evaluation, and rate of major histological response was equal in both arms. Toxicity was increased by panitumumab with regard to thromboembolic events and skin toxicity. Patients with tumour EGFR, HER2 or MET expression had shorter progression-free and overall survival. FISH positivity for these markers was associated with shorter survival independent of therapy. High levels of soluble EGFR in particular predicted poor survival in the panitumumab arm. CONCLUSION: The addition of panitumumab to ECX did not improve downstaging of locally advanced EGC. Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy. CLINICALTRIALS.GOV: NCT01234324.

Prospective randomized comparison of minilaparoscopy and percutaneous liver biopsy: diagnosis of cirrhosis and complications.

BACKGROUND AND AIMS: Liver cirrhosis represents an advanced stage of hepatic fibrosis characterized by distortion of organ architecture and formation of regenerative nodules. Retrospective series reported percutaneous liver biopsy to miss cirrhosis in about 30%. The aim of this study was to prospectively compare diagnostic sensitivity regarding the detection of cirrhosis and the complication rates of percutaneous versus minilaparoscopic liver biopsy in chronic liver disease. METHODS: Eight hundred fifty-seven patients were randomized to percutaneous (415) or to minilaparoscopic liver biopsy (442). Macroscopic liver evaluation was documented as normal, fibrosis, or cirrhosis. Liver specimens were assessed blindly according to the modified Ishak score. RESULTS: Demographic and clinical data of procedure groups were comparable. Histologic grading alone diagnosed cirrhosis in 22.3% (n=85) of liver specimens obtained by percutaneous route compared with 26.0% (n=98) obtained by minilaparoscopy (P=0.270). By combining macroscopy and histology, minilaparoscopic staging diagnosed a significantly higher rate of liver cirrhoses with 33.8% (n=127) compared with percutaneous route with 22.3% (n=85) (P=0.001). Analysis of minilaparoscopic data revealed that 33 of the 128 cirrhoses were diagnosed by inspection only, suggesting a 26% underestimation of cirrhosis by histology alone. Severe complications occurred in 1.0% (n=4) of percutaneous and in 0.2% (n=1) of minilaparoscopic procedures (P=0.025). CONCLUSIONS: Minilaparoscopic evaluation based upon the combined macroscopic and histologic assessment is more sensitive with regards to the detection of cirrhosis and has a comparable safety profile.

Mini-laparoscopically guided percutaneous gastrostomy and jejunostomy.

BACKGROUND: Percutaneous endoscopic tube placement can be problematic under certain circumstances: absence of transillumination of the abdominal wall, percutaneous jejunostomy in patients with a PEG tube and recurrent aspiration, enteral feeding access after gastrectomy, and obstruction of the upper GI tract. As an alternative in these problematic situations, a technique was developed for placing feeding tubes under visual control by using mini-laparoscopy. METHODS: Placement of a feeding tube with mini-laparoscopy with the patient under conscious sedation was considered for 17 patients in whom standard PEG placement was impossible. Techniques used were the following: combined mini-laparoscopy/endoscopy for placement of a percutaneous gastrostomy or jejunostomy, and mini-laparoscopic-guided direct tube placement in cases of obstruction of the upper GI tract. OBSERVATIONS: In 13 patients, mini-laparoscopic-assisted tube placement was successful. In 4 patients, adhesions or peritoneal carcinomatosis prevented laparoscopic visualization of the stomach or small bowel. The combined mini-laparoscopic/endoscopic approach allowed a successful insertion of gastric tubes in 6 patients and jejunal tubes in 4 patients. Direct insertion of a percutaneous endoscopic jejunostomy tube without enteroscopy was feasible in all 3 patients with obstruction of the upper GI tract. No complication occurred. CONCLUSIONS: Mini-laparoscopy-assisted tube placement is a simple and safe alternative when endoscopic percutaneous tube placement is problematic or not feasible.